Modeling a pediatric brain tumor

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Science  15 Mar 2019:
Vol. 363, Issue 6432, pp. 1188-1189
DOI: 10.1126/science.363.6432.1188-e

Childhood cancers often harbor somatic mutations in genes encoding epigenetic regulators such as histones. For example, about 80% of diffuse intrinsic pontine gliomas (DIPGs), which are aggressive pediatric brainstem tumors, have a specific mutation (lysine-27 substituted with methionine, or K27M) in histone H3.3. This mutation impairs the repressive effect of the histone on transcription, but how it contributes to tumor development has been unclear. By analyzing mouse models, Larson et al. found that the H3.3 K27M mutation transiently stimulated self-renewal of neural stem cells on its own. When this mutation was combined with two other cancer genes, mice developed brainstem gliomas resembling human DIPG. These tumors showed increased expression of genes associated with neural development, supporting the hypothesis that pediatric gliomas are developmental disorders.

Cancer Cell 35, 140 (2019).

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